PROJECT SUMMARY/ABSTRACT This is an application for a Mentored Clinician Scientist Research Career Development Award. The goal of the proposed project is to provide the candidate with advanced skills needed to transition to an independent translational investigator with focus on accurate prognostic biomarkers and development of a tailored treatment algorithm in HCC. To facilitate this long-term career goal the candidate will examine multiple imaging, clinical and blood-based biomarkers, and investigate the role of liquid biopsy in HCC progression in liver transplant-eligible patients. The candidate proposes a comprehensive training plan, combining didactic instruction overseen by her mentors, formal coursework, participation in applied training experiences with individual mentors/advisors, and supervised performance of relevant laboratory techniques. The proposed study will enroll HCC patients listed for liver transplantation and follow until the time of transplantation or disease progression and death. She will identify the determinants contributing to the disparate outcomes by including novel functional imaging, clinical risk factors and circulating biomarkers including circulating tumor cells, immune cells and tumor DNA. This application provides a more tailored approach to patient management in the limited time available, to offer effective therapy to patients who are challenged with a lethal cancer and end-stage liver disease. It would also improve liver transplant organ allocation, thus improving overall therapeutic value for liver transplant recipients.